The Keatley Foundation made a generous $10,000 donation to the Kimmel Cancer Center. Events like their second annual Beef and Beer contributed to this generous donation. The Keatley Foundation was created by Bob Lyons during his treatment at Jefferson Hospital. The foundation name comes from the street name where Bob lives. According to Bob, That street sign was “The sign that I started my road to recovery on every morning, gaining strength to take a few more steps towards that street sign on the corner each day”. For more about Bob’s story please see the following Jefferson Hospital blog post.

The study published in the open access online journal PLoS ONE tested the use of intravenous ascorbic acid (vitamin C) three times a week over an eight week cycle in nine patients with metastatic stage IV pancreatic cancer in addition to standard gemcitabine and erlotinib chemotherapy regimens.

“These initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients,” wrote the team of researchers from the Kimmel Cancer Center at Jefferson as well as the National Institutes of Health (NIH). “This combination with the observed response to treatment suggests the need for a phase II study of longer duration.”

Daniel A. Monti, MD, Executive and Medical Director of the Jefferson-Myrna Brind Center of Integrative Medicine and lead author of the study said, “We are pleased and encouraged by these results.”

Dr. Monti added, “it is a Jefferson priority to study promising therapies for pancreatic cancer. It is crucial to explore anything that might feasibly give these patients an edge. We are now actively enrolling eligible patients into the Phase II trial.”

Smoking cessation at least two weeks prior to surgery, gown and glove change prior to skin closure, and using clippers over razors to shave the surgical area are some of the measures that helped reduced infection rates, according to the study published in the October 26 online issue of the Journal of Surgical Research.

In a retrospective study, Harish Lavu, M.D., assistant professor in the Department of Surgery at Thomas Jefferson University, and colleagues analyzed clinical data from 233 consecutive Whipple procedures—also known as a pancreaticoduodenectomy, an operation to treat benign and malignant diseases of the pancreas—from October 2005 to May 2008 on patients who underwent routine preoperative preparation (RPP). That preparation is less comprehensive than the 12 measure surgical care bundle. For instance, it uses a razor for hair removal and iodine skin preparation and does not include smoking cessation.

They compared those rates to 233 consecutive Whipple procedures performed from May 2008 to May 2010 following the implementation of the surgical care bundle.

The researchers found a 49 percent reduction in wound infections in the surgical care bundle group (7.7 percent) compared to the RPP group (15 percent). The difference was statistically significant.

“It is typically quite difficult to achieve a 50 percent reduction in an adverse outcome,” Dr. Lavu says. “We can make a significant impact on lowering wound infection in patients undergoing this surgery by using this set of guidelines.”

Wound infection rates for Whipple procedures are historically higher and more common than in other procedures. Infections can be painful and require reopening the incision, which can ultimately leave scarring. Also, if an infection is not identified quickly, it can spread and patients can become very ill.

Two standout measures, Dr. Lavu says, are the gown and glove change prior to skin closure and intraoperative wound edge protection, which separates edges of the incision from contact with visceral contents, instruments and gloves during the procedure. And, like past studies have shown, using chlorhexidine-alcohol for skin preparation, instead of iodine, helps lower the risk of wound infections.

“The preoperative and post operative briefings alone, which are now being instituted in many American hospitals, reduce complications simply by improving communication among members of the health care team,” Dr. Lavu says.

“While some procedures at certain hospitals include a similar surgical bundle care, Jefferson’s is the first one, to the author’s knowledge, that has been implemented for pancreatic surgery.”

“Now it is the standard of care here, and we are trying to move the surgical care bundle as it applies to other kinds of surgery, even in other departments at Jefferson,” Dr. Lavu says.

October 2011 marks 20 years of exceptional cancer care and research at KCC

From October forward, the Kimmel Cancer Center at Jefferson (KCC), a National Cancer Institute-designated cancer center, is celebrating 20 years of service to the community and the groundbreaking cancer research from the scientists and physicians who’ve provided an invaluable contribution to medical science and healthcare.

“With our multidisciplinary approach, KCC’s team of clinicians and researchers has continued to put their best feet forward to provide excellent, stand-out personalized care for cancer patients in the Philadelphia region and beyond and uncover new pathways to better prevent, diagnose and treat the disease,” he added.

It was October 1991 when the Jefferson Cancer Institute opened, with the dedication of the Bluemle Life Science Building on the Thomas Jefferson University campus. Four years later, with the awarding of a Cancer Center Support Grant, the National Institutes of Health National Cancer Institute (NCI) officially recognized it as one of only 54 NCI-designated cancer centers in the U.S. at the time. The institute took its current name in 1996 when businessman and philanthropist Sidney Kimmel made a generous donation to the institute to expand its research activities.

The donation to Jefferson is not a “gift,” but “an investment for humanity,” Mr. Kimmel told the Philadelphia Inquirer in 1996. “I really believe we’re going to have a breakthrough” in cancer research.

Dr. Pestell, who became director in 2005, has made significant contributions to understanding cell cycle regulation and the aberrations that can lead to cells turning cancerous. His work identified new molecular markers, and new targets for cancer treatment. An internationally renowned expert in oncology and endocrinology, Dr. Pestell’s record of research funding is outstanding, securing substantial National Institutes of Health grants for the KCC.

Two recent clinical trials have resulted in the addition of new procedures at Thomas Jefferson University Hospital. For example, in the Department of Urology, under chairman Leonard Gomella, M.D, a bladder cancer diagnostic tool using an imaging agent and blue light technology is now helping physicians better detect tumors along the bladder lining. Also, a new, two-step approach to half-match bone marrow transplants (where a patient can use a sibling or parent as a donor) developed by Chair of Medical Oncology Neal Flomenberg, M.D., is proving to be a success for blood cancer patients whose options were otherwise limited. Jefferson is the only hospital in the region performing half-match procedures.

Since being appointed as chair of the Department of Radiation Oncology in 2010, Adam Dicker, M.D., Ph.D., has led extensive clinic renovations and the ongoing addition of new technologies. That includes Bodine’s recently acquired radiation therapy equipment for head and neck and prostate cancer patients and an upcoming radiosurgey instrument designed to deliver higher doses of radiation to smaller areas. Bodine’s state-of-the-art brachytherapy suite is also set to open in early 2012.

Last year, Charles J. Yeo, M.D., Chair of Surgery, performed his 1,000th Whipple procedure. The Whipple procedure is a major surgical operation involving removal of portions of the pancreas, bile duct and duodenum, and is typically performed to treat malignant tumors involving the pancreas, common bile duct or duodenum. Jefferson’s surgery department treats more pancreatic cases than anywhere in the region.

Thomas Jefferson University Hospital is consistently ranked in the top 50 best hospitals for treating cancer in America (#31 in 2011) in U.S. News and World Report. What’s more, the hospital has moved up more than 20 places in the past five years for cancer.

Hwyda Arafat, M.D., Ph.D., associate professor of Surgery at Jefferson Medical College of Thomas Jefferson University

Pancreatic cancer researchers at Thomas Jefferson University have shown, for the first time, that blocking a receptor of a key hormone in the renin-angiotensin system (RAS) reduces cancer cell growth by activating the enzyme AMPK to inhibit fatty acid synthase, the ingredients to support cell division.

With that, a new chemopreventive agent that inhibits the angiotensin II type 2 receptor—never before thought to play a role in tumor growth—could be developed to help treat one of the fastest-moving cancers that has a 5-year survival rate of only 5 percent.

Angiotensin II (AngII) is the principal hormone in the RAS that regulates our blood pressure and water balance; it has two receptors: type 1 and type 2. AngII is also generated actively in the pancreas and has been shown to be involved in tumor angiogenesis.

Previous studies have pointed to the hormone’s type 1 receptor as the culprit in cancer cell proliferation and tumor inflammation; however, the idea that type 2 had any effect was never entertained.

By looking at pancreatic ductal adenocarcinoma (PDA) cells in vitro, Jefferson researchers discovered that the type 2 receptor, not just type 1, mediates the production of fatty acid synthase (FAS), which has been shown to supply the cell wall ingredients necessary for cancer cells to multiply.

FAS was previously identified as a possible oncogene in the 1980s. It is up-regulated in breast cancers and is indicator of poor prognosis, and thus believed to be a worthwhile chemopreventive target.

“AngII is not just involved in cell inflammation and angiogenesis; it’s involved in tumor metabolism as well,” said Dr. Arafat, a member of the Kimmel Cancer Center at Jefferson. “It promotes FAS with both receptors, which makes the tumor grow.”

“Blocking the type 2 receptor reduces PDA cell growth with the activation of AMPK, revealing a new mechanism by which chemoprevention can exploit,” she added. “In fact, maybe combined blocking of the two receptors would be more efficient than just blocking one receptor.”

AMPK, or adenosine monophosphate-activated protein kinase, is the focus of several agents today, including ones for diabetes and related metabolic diseases. It is a master metabolic regulator for cells that is activated in times of reduced energy availability, like starvation. Activation of AMPK has been shown to improve energy homeostasis, lipid profile and blood pressure. The enzyme also activates a well-known tumor suppressor, p53.

“The main thing is activation of AMPK in tumor cells,” said Dr. Arafat. “AMPK is the perfect candidate as it regulates multiple targets that both halt tumor cell division and activate programmed cell death. Although it is yet to be determined how the type 2 receptor imposes deregulation of AMPK activity, identification of the type 2 receptor as a novel target for therapy is very exciting”

Next, Dr. Arafat and fellow researchers are proposing to take this research into animal studies. They hope to target the receptors early on in the disease to better understand its prevention capabilities and also study its treatment potential. Considering pancreatic cancer is typically detected in later stages, finding better ways to treat cases that have progressed further along would be of great benefit to patients.

Medical physicists at Thomas Jefferson University and Jefferson’s Kimmel Cancer Center have demonstrated a new real-time tumor tracking technique that can help minimize the amount of radiation delivered to surrounding healthy tissue in a patient—up to 50 percent less in some cases—and maximize the dose the tumor receives.

Respiratory and cardiac motions have been found to displace and deform tumors in the lung, pancreas, liver, breast, and other organs. Because of this, radiation oncologists must expand the margin during radiotherapy, and consequently a large volume of healthy tissue is irradiated, and critical organs adjacent to the tumor are sometimes difficult to spare.

In an effort to shrink that margin, Jefferson researchers developed a new 4D, robotic technique that better predicts and continuously tracks tumors during radiotherapy, preventing unnecessary amounts of radiation from being administered to unnecessary areas. Thus, critical organs and tissues are spared; cancer treatment is potentially improved; and side effects are decreased.

Published in the online February 1 issue of Physics in Medicine and Biology journal, the study was co-authored by Ivan Buzurovic, Ph.D., a medical physics resident and researcher in the Department of Radiation Oncology at Jefferson Medical College at Thomas Jefferson University, and Yan Yu, Ph.D., director of Medical Physics at Thomas Jefferson University.

In this technique, the robotic system—programmed with the proposed algorithms developed by Jefferson researchers—is automatically adjusted so that the position of the tumor remains stationary during treatment.

“The advantage of this novel approach in radiation therapy is that the system is able to predict and track tumor motion in three-dimensional space,” said Dr. Buzurovic. The technique can compensate both tumor motion and residual errors during patient treatment, he added.

When active tracking was applied and tumor motion was up to 1.5 cm, irradiated planning target volume (PTV) was 20 to 30 percent less for medium size tumors and more than 50 percent for small size tumors. For tumor motion range up to 2.5 cm, irradiated PTV was two times smaller when tracking is applied.

“The proposed robotic system needs 2 seconds to start tracking with the high precision level. The tracking error was less than 0.5 mm for regular breathing patterns and less than 1 mm for highly irregular respiration,” said Dr. Buzurovic. “Prediction algorithms were developed to predict tumor motion and to compensate errors due to delay in the system response.”

The study findings suggest that the use of tumor tracking technology during radiotherapy treatment for lung cancer would result in significant reduction in dose to the healthy tissue, potentially decreasing the probability or severity of side effects, co-author Dr. Yu said.

With this new technique, radiation oncologists would be able to administer more radiation and faster to the tumor than conventional methods, said Adam P. Dicker, M.D, Ph.D., professor and chairman of the Department of Radiation Oncology at Thomas Jefferson University.

“If we shrink our margin by this new robotic technique, then we can bring larger doses to tumors,” Dr. Dicker said. “And a higher dose means a better cure in lung cancer, for instance.”

Researchers from Department of Radiation Oncology at the University of Michigan Hospital in Ann Arbor, Mich., and Brody School of Medicine at East Carolina University, Greenville, N.C., were also involved in the study.

The researchers’ method, demonstrated in extensive computer simulation, can be applied to two commercially available robotic treatment couches.

The levels of an inflammatory chemokine were significantly elevated in patients with pancreatic cancer who were extremely obese, according to research conducted by scientists at the Jefferson Pancreatic, Biliary and Related Cancers Center. They presented their data at the 5th Annual Academic Surgical Congress, held in San Antonio.

Studies have shown that obesity is correlated with inflammation. Similarly, studies have also shown that inflammation contributes to the tumor progression of pancreatic ductal adenocarcinoma (PDA). This study looks at the role of monocyte chemoattractant protein-1 (MCP-1), a marker of inflammation, in obese patients with pancreatic cancer.

An herb recently found to kill pancreatic cancer cells also appears to inhibit development of pancreatic cancer as a result of its anti-inflammatory properties, according to researchers from the Kimmel Cancer Center at Jefferson. The data were presented at the AACR 100th Annual Meeting 2009 in Denver. (Abstract #494)

Nigella sativa

Thymoquinone, the major constituent of the oil extract from a Middle Eastern herbal seed called Nigella sativa, exhibited anti-inflammatory properties that reduced the release of inflammatory mediators in pancreatic cancer cells, according to Hwyda Arafat, M.D., Ph.D., associate professor of Surgery at the Jefferson Medical College of Thomas Jefferson University and a member of the Jefferson Pancreatic, Biliary & Related Cancers Center.

Nigella sativa seeds and oil are used in traditional medicine by many Middle Eastern and Asian countries. It helps treat a broad array of diseases, including some immune and inflammatory disorders, Dr. Arafat said. Previous studies have also shown it to have anti-cancer effects on prostate and colon cancers.

A combination of Sorafenib and Vitamin K had an effect in vitro on both human pancreas cancer and hepatocellular carcinoma, according to researchers from the Kimmel Cancer Center at Jefferson. Data from the two studies were presented at the AACR 100th Annual Meeting 2009 in Denver. (Abstract #5470 and #5483)

Vitamin K1 or Vitamin K2, plus Sorafenib (Nexavar) each have shown activity against the growth of human cancer cells by inhibiting the extracellular signal-regulated kinase (ERK) pathway according to Brian Carr, M.D., Ph.D., a professor of Medical Oncology at the Jefferson Medical College of Thomas Jefferson University. ERK plays a major role in cell growth of cancers.

Although Sorafenib has demonstrated success at extending survival in patients with hepatocellular carcinoma (HCC, or primary liver cancer), hand-foot syndrome is a common adverse effect that affects approximately 20 percent of patients who receive the drug. It typically manifests as painful sores on the soles of patients’ feet that can prevent the patients from walking, Dr. Carr said. Profound tiredness and weight loss is also seen in at least 30 percent of patients.

An herb used in traditional medicine by many Middle Eastern countries may help in the fight against pancreatic cancer, one of the most difficult cancers to treat. Researchers at the Kimmel Cancer at Jefferson in Philadelphia have found that thymoquinone, an extract of Nigella sativa seed oil, blocked pancreatic cancer cell growth and killed the cells by enhancing the process of programmed cell death.

While the studies are in the early stages, the findings suggest that thymoquinone could eventually have some use as a preventative strategy in patients who have gone through surgery and chemotherapy or in individuals who are at a high risk of developing cancer.

If lung cancer and heart disease aren’t bad enough, cigarette smokers are also at higher risk for developing, among other things, pancreatic cancer. Now, researchers at the Kimmel Cancer at Jefferson in Philadelphia have preliminary evidence indicating one possible reason why. Data being presented April 13, 2008 during the Annual Meeting of the American Association for Cancer Research shows that they have found that nicotine in cigarettes increases the production of a protein that is known to promote cancer cell survival, invasion and spread.

According to Hwyda Arafat, M.D., Ph.D., associate professor of Surgery at Jefferson Medical College of Thomas Jefferson University, the protein, osteopontin, is found in a variety of fluids in the body, such as plasma, cerebrospinal fluid, synovial fluid and breast milk. Osteopontin is also present in different organs and plays an important role during embryonic development. Recent studies have demonstrated that osteopontin levels are significantly higher in the blood and pancreas tissue of pancreatic cancer patients. The protein, when over-produced, can make cancer cells more likely to become metastatic.

Researchers at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia are inching closer to understanding how common blood pressure medications might help prevent the spread of pancreatic cancer. They have found in the laboratory that one type of pressure-lowering drug called an angiotensin receptor blocker inhibits pancreatic cancer cell growth and causes cell death.

In earlier work in the laboratory, Hwyda Arafat, M.D., Ph.D., associate professor of Surgery at Jefferson Medical College, and her team showed that angiotensin receptor blockers may help reduce the development of tumor-feeding blood vessels, a process called angiogenesis. Other studies have linked a lower incidence of cancer with the use of angiotensin blocking therapies. Such drugs, she says, may become part of a novel strategy to control the growth and spread of cancer.

It’s against this background that Jefferson, Jefferson’s Kimmel Cancer Center and the Pancreatic Cancer Action Network (PanCAN), a national advocacy organization, are sponsoring a pancreatic cancer symposium on Saturday, April 5, 2008 on the Thomas Jefferson University campus. The program will be held in the Dorrance H. Hamilton Building, 1001 Locust Street, beginning at 9 a.m. It is free to the public.

A protein that helps prevent a woman’s body from rejecting a fetus may also play an important role in enabling pancreatic cancer cells to evade detection by the immune system, allowing them to spread in the body.

Researchers at Jefferson’s Kimmel Cancer Center in Philadelphia found that the metastatic cancer cells in the lymph nodes of patients with pancreatic cancer produce enough of the protein, IDO, to essentially wall-off the immune system’s T-cells and recruit cells that suppress the immune system’s response to the tumor. The findings might mean not only a better way to detect pancreatic cancer spreading to lymph nodes, but also could enhance tumor immune therapy strategies against the fast-moving, deadly disease.

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